### Page 1 of 10 EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE

PETITIONS PUBLISHED IN THE FEDERAL REGISTER

Interregional Research No. 4, Rutgers, The State University of New Jersey, 500 College Road East, Suite 201

- W, Princeton, NJ 08540

PP# 6E8446

EPA has received a pesticide petition ( PP# 6E8446 ) from Interregional Research Project Number 4 (IR

- 4), Rutgers, The State University of New Jersey, 500 College Road East, Suite 201 W, Princeton, NJ 08540 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 34 6a(d), to amend 40 CFR part 180 by establishing a

to lerance for residues of e tofenprox, [2

- (4

- ethoxyphenyl)

- 2

- methylpropyl 3

- phenoxybenzyl ether], including its metabolites and degradates, in or on f ungi, edible, group 21 at 3.0 parts per million ( ppm ) and to amend the tolerance for a ll food commodities (in cluding feed commodities)

not otherwise listed from 5.0 ppm to 0. 40 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d)(2) of FDDCA; however, EPA has not fully evaluated the sufficienc y of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The plant metabolis m of e tofenprox is adequately understood in four diverse crops: rice, grapes, oilseed rape and lettuce. The parent compound, e tof enprox
, and the metabolite , α

- CO [ 2

- (4

- ethoxyphenyl)

- 2

- methylpropyl 3

- phenoxybenzoate ]

, accounted for the majority of re sidues extracted in all crops. The metabolism of e tofenprox in plants is understood for the purpos es of the proposed

tolerances. Even though t he parent compound, e tofenprox

, and the metabolite

, α

- CO

, are the residues of

concern for tolerance setting purpos es, EPA has previously determined tolerances are applicable for the parent compound, e tofenprox, only.

2. Analytical method

Etofenprox + Piperonly Butoxide: Magnitude of the Residue on Mushroom

In the magnitude of residue on mushroom study for Etofenpr ox + piperon y l butoxide (PBO) study t he samples were analyzed using a working method very similar to the reference methods, “Analytical Method Validation for the Determination of Etofenprox and alpha

- CO in Rice and Rice Straw”, Wildlife International, Ltd. 236C

- 136 (Jon A. MacGregor and Willard B. Nixon), 3/15/2006, and “Determination of Pyrethrins and Piperonyl Butoxide (PBO) in Crops”, Golden Pacific Laboratories (Mary R. Huebner),

GLP

- MTH

- 074, 5/24/2010.

Residues of etofenprox and alpha

- CO were extracte d from mushroom with acetone. Following extraction, an aliquot of the extract was purified by a graphitized carbon black solid phase extraction. The purified extract was concentrated to dryness, reconstituted in acetonitrile: water:formic acic, and then submitted to LC/MS/MS analysis.

Residues of PBO were extracted from mushroom with acetonitrile. Following extraction, an aliquot of the extract was diluted and then submitted to LC/MS/MS analysis. Method suitability was evaluated both prior to sample an alysis and concurrently with sample analysis. Recoveries were in the ranges 85

- 101% for etofenprox, 82

- 100% for alpha

- CO, and 86

- 98% for PBO.

### Page 2 of 10 The LOD for the respective methods were calculated for this final report to be 0.00171 ppm (etofenprox),

0.0017 9 ppm (alpha

- CO), and 0.00107 ppm (PBO), and the LOQs were calculated to be 0.00513 ppm (etofenprox), 0.00537 ppm (alpha

- CO), and 0.00320 ppm (PBO), using the method described in Roy

- Keith Smith's Handbook of Environmental Analysis, Fourth Edition, Genium Publishing Corporation. The lowest level of method validation (LLMV) for mushroom was 0.010 ppm for each analyte. Analytical sets typically consisted of calibration standards, unfortified controls, fortified controls, and treated samples. A

calibration standard was injected at the beginning and end of each analytical set.

Etofenprox: Magnitude of the Residue on Orange, Pasture Grass, and Leaf Lettuce

In the magnitude of the residue on orange, pasture grass, and leaf lettuce study t he samples were analyzed using a working method very similar to the reference method, “Analytical Method Validation for the Determination of Etofenprox and α

- CO in Rice and Rice Straw” Wildlife International, Ltd. 236C

- 136, Jon A. MacGregor and Willard B. Nixon, 3/15/2006 . Results for α

- CO were reported in parent equivalents.

Residues of etofenprox and its metabolite α

- CO were extracted from crop matrices with acetone. Following extraction, an aliquot of the extract was purified by a graphitized carbon black and HAX (gras s only) solid phase extraction. The purified extract was concentrated to dryness, reconstituted in acetonitrile:water:formic acid, and then submitted to LC/MS/MS analysis.

Method suitability was evaluated both prior to sample analysis and concurrently wi th sample analysis. Recoveries of etofenprox were in the range 79

- 101% for orange fruit, 80

- 94% for grass forage, and 77

- 99% for leaf lettuce. Recoveries of α

- CO were in the range 85

- 100% for orange fruit, 67

- 96% for grass forage, and 81

- 104% for leaf let tuce.

The LOD and LOQ for the method on orange fruit and pasture grass forage were statistically calculated

and t he results are shown in the table below:

Commodity Etofenprox α

- CO LOD (ppm) LOQ (ppm) LOD (ppm) Orange Fruit 0.00103 0.00309 0.00168 0.00505

Pasture Grass Forage 0.00110 0.00329 0.00303 0.00908

Leaf Lettuce

--- --- --- ---

The LOD and LOQ were not calculated for leaf lettuce because there was not sufficient data at the LLMV. The lowest level of method validation (LLMV) for orange, pasture grass, & leaf lettuce was 0.01 ppm for etofenprox and α

- CO. Analytical sets typically consisted of calibration standards, unfortified controls, fortified controls, and treated samples. A calibration standard was injected at the beginning and end of each analytical set.

3. Magnitude of residues

Etofenprox + Piperon y l Butoxide: Magnitude of the Residue on Mushroom

Three trials were conducted on white button mushrooms, and the fourth was conducted on oyster mushrooms. In the oyster mushroom trial a nd in two of the three white button mushroom trials, applications were made with a fogger, whereas in the remaining white button mushroom trial, applications were made as surface sprays.

### Page 3 of 10 In the CA26 and MD07 trials conducted on white button mushrooms, fog ging applications were made at

0.046

- 0.047 lb etofenprox/10,000 cubic feet and 0.183

- 1.188 lb PBO/10,000 cubic feet, whereas in the MD06 trial also conducted on white button mushrooms, applications were sprayed onto the walls, floor, and mushroom trays at a rate of 0.0225 lb etofenprox/1000 square feet and 0.090 lb PBO/1000 square feet in a spray volume of 42

- 44 gallons/acre. In the CA25 trial conducted on oyster mushrooms, fogging applications were made at 0.047 lb etofenprox/10,000 cubic feet and 1.188 lb PBO/10,000 cubic feet.

All applications were made using appropriate spray equipment, and the spray or fogging volume was sufficient to provide adequate dispersal of the test substance.

The proposed tolerance for combined residues of the parent compound, e tofenprox

, and its metabolites or degradates in or on fungi, edible, group 21 is 3.0 ppm . These proposed tolerances are protective of the U.S. population and all subgroups.

The residues of etofenprox were in the range <0.010 ppm to 1 .7 ppm. No detectable residues of alpha

- CO were found in white button mushroom samples, but residues as high as 0.068 ppm (calculated as parent equivalent) were found in oyster mushroom samples. The residues of PBO were in the range <0.010 ppm to 3.2 ppm

.

Etofenprox: Magnitude of the Residue on Orange, Pasture Grass, and Leaf Lettuce

Magnitude of residue data were collected on oranges, pasture grass, and leaf lettuce from one field trial located in NAFTA Region X. Six sets of ground ULV fogging app lications of the undiluted test substance

5

- 7 days apart were made to the treated plots within 4 hours of sunrise or sunset. Each set of applications consisted of 2 consecutive applications, each at the maximal labeled rate. The applications to the pasture grass and leaf lettuce plots were made simultaneously. The application rates ranged from 0.00652 to 0.00756 lb ai/A per application for orange and 0.00661 to 0.00723 lb ai/A per application for pasture grass and leaf lettuce. The total application rates f or each application set ranged from 0.0131 to 0.0149 lb ai/A for orange and 0.0137 to 0.0140 lb ai/A for pasture grass and leaf lettuce. A total rate of 0.0834 lb ai/A was applied to the orange plot and 0.0829 lb ai/A was applied to the pasture grass and l eaf lettuce plots. All applications were made using appropriate spray equipment, and the spray volume was sufficient to provide adequate dispersal of the test substance.

There were no residues found in any orange fruit sample above 0.01 ppm for etofenpr ox or the α

- CO metabolite. Residues of ranged from 0.036 to 0.22 ppm for etofenprox and <0.01 to 0.041 ppm for α

- CO in pasture grass forage samples taken at <12 hours after each application set. The total residues of ranged from <0.01 to 0.22 ppm for etof enprox leaf lettuce samples taken at <12 hours after each application set.
There were no residues of α

- CO above 0.01 ppm in any leaf lettuce sample. Residues of both etofenprox
and α

- CO declined in grass forage samples collected 7 days after the last appli cation set and then remained similar from 7 to 20 days PHI.

B

. Toxicological Endpoints

A summary of the toxicological endpoints for etofenprox used for human risk assess ment is shown in the following t able:

Doses and Toxicological Endpoints for Etofenprox

Exposure/Scenario Dose Used in Risk Assessment, Interspecies,

Intraspecies and any

Traditional UF FQPA SF and Level of

Concern for Risk Assessment Study and Toxicological Effects

Acute Dietary (females 13

- 49 years of age) Not selected NA No toxicological endpoint attributable to a single exposure was

### Page 4 of 10 Doses and Toxicological Endpoints for Etofenprox

Exposure/Scenario Dose Used in Risk Assessment, Interspecies,

Intraspecies and any

Traditional UF FQPA SF and Level of

Concern for Risk Assessment Study and Toxicological Effects

identified in the available toxicology

studies. Acute Dietary (General population including infants and children) Not selected NA No toxicological endpoint attributable to a single exposure was identified in the available toxicology

studies. Chronic Dietary (All populations) NOAEL = 3.7 mg/kg/day

Chronic RfD = 0.037 mg/kg/day. FQPA SF = 1x cPAD = Chronic RfD/Special FQPA

SF = 0.037 mg/kg/ day. Combined Chronic Toxicity/ Carcinogenicity Study in Rat MRID No. 40449707) LOAEL = 25.5 mg/kg/day based on increased thyroid weights. Related to increased liver weights and histopathology changes in liver and thyroid that occurred at the hig her

dose.

Incidental Oral Short

- Term (1

– 30 days) NOAEL =100 mg/kg/day

UF = 100 LOC for MOE = 100 Developmental Toxicity in Rabbit (MRID No. 45210602) LOAEL = 300 mg/kg/day based on decreased body weights, body weight gains, and food consumption (maternal toxicity).

Incidental Oral Intermediate

Term (1

- 6 months) NOAEL = 20 mg/kg/day

UF = 100 LOC for MOE = 100 Subchronic Oral Toxicity in Rat (MRID No. 40449703) LOAEL = 120 mg/kg/day based on decreased body weight gain,

increased liver and thyr oid weights with corresponding histopathology, changes in hematology and clinical chemistry.

Dermal (All durations) NA NA No systemic toxicity was identified

in the dermal 28

- day study; Highest Dose Tested was 1,000 mg/kg/day.

Inhalation (All durations ) NOAEL =10.6 mg/kg/day

UF = 100 LOC for MOE = 100

Residential

LOC for MOE = 100 Occupational 13

- Week Inhalation Toxicity in Rat (MRID No. 40449705) LOAEL = 52.3 mg/kg/day based on organ weight changes and histopathological changes in liver, adrenals and thyroid.

Cancer (oral, dermal, inhalation) Classification: ``Not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone

homeostasis.''
UF = uncertainty factor, FQPA SF = any additional safety factor retained due to concerns unique to the FQPA, NOAEL = no observed adverse effect level, LOAEL = lowest observed adverse effect level, PAD = population adjusted dose (a = acute, c = chronic) RfD = ref erence dose, MOE = margin of exp osure, LOC = level of concern, NA = Not Applicable

C. Exposure Assessment

1. Dietary Exposure

a. Acute exposure

Acute dietary risk assessments are performed for a food

- use pesticide if a toxicological study has indicated the possibility of an effect of concern occurring as a result of a one day or single exposure. An acute risk assessment was not performed. No toxicological endpoint attributable to a single (acute) dietary exposure

was identified.

### Page 5 of 10 b. Chronic exposure

A chronic dietary risk assessment was conducted for e tofenprox use on fungi, edible, group 21 and use on food/feed commodities following ULV fogging applications using the Dietary Exp osure Evaluation Model ( DEEM

- FCIDTM, Version 4.02 ) which uses food translations base on EPA/USDA FCID recipe set as of August 2014. Screening level estimates of e tofenprox in water (1.2 ppb) were provided by the Etofenprox Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessment for the Section 3

R egistration Action

– Mosquito Adulticide Over Crop L and dated 04/16/13 DP Barcode D396534. In addition, food/feed commodities identified in DP Barcode D396534 requiring tolerance values different than 5 ppm were used in the current dietary risk assessment since the purpose is to amend the overall food/feed tolerance from 5 ppm to 0.4 ppm unless otherwise specified.

The concentration of e tofenprox on food/feed commodities is assumed at the proposed tolerance level of

0. 4 ppm unless otherwise specified in DP Barcode D396534. Percent crop treated values identified in DP Barcode D396534 were used for this chronic dietary assessment

. The chronic dietary risk estimates are

below HED’s level of concern for the general U.S. population and all population subgroups. The most highl y exposed population subgroup ( 4.6 % of the Rfd ) was children 1

- 2 years old.

Summary of Chronic Dietary (Food + Drinking Water) Exposure and Risk for Etofenprox

Population Subgroup Exposure (mg/kg bw/day) Percent of Rfd 1

US population 0.000421 1.1%

All infants ( < 1 year old) 0.000537 1.5%

Children (1

- 2 years old) 0.001689 4.6%

Children (3

- 5 years old) 0.001216 3.3%

Children (6

- 12 years old) 0.000662 1.8%

Youth (13

- 19 years old) 0.000367 1.0%

Adults (20

- 49 years old) 0.000304 0.8%

Adults (50+ years old) 0.000297 0.8%

1 Rfd = 0.037 mg/kg/day

c. Cancer

Et ofenprox has been classified as “ Not likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone homeo stasis.” In 1989, the EPA classified e tofenprox as a “ Gro up C Possible Human Carcinogen” based on thyroid tumors in rats. In 1996

, the EPA evaluated additional information submitted by the registrant, Mitsui Toatsu, regarding the carcinogenic potential of e tofenpr ox . Its objective was to demonstrate a threshold mechanism for the thyroid tumors in rats. In 2005, an additional 4

- week dietary investigative study on thyroid function and hepatic microsomal enzyme induction in rats was reviewed by the EPA. In 2005, the A gency considered if the additional study along with the previously submitted data provided sufficient informati on to support re

- evaluation of e tofenprox's carcinogenicity status. In consideration of these new data, and in accordance with the EPA Final Guid elines for Carcinogen Risk
Assessment, e tofenprox was classified as “ Not likely to be carcinogenic to humans at doses that do not

alter rat thyroid hormone homeostasis.” This decision was based on the following considerations:

i. Treatment

- related thyroid fol licular cell tumors were seen in both male and female rats at 4,900 ppm, which was considered to be adequate, and not excessive, to assess carcinogenicity;

ii. No treatment

- related tumors were seen in male or female mice when tested at a dose that was

consider ed adequate to assess carcinogenicity;

iii. There is no mutagenicity concern for e tofenprox fro m in vivo or in vitro assays;

### Page 6 of 10 iv. The non

- neoplastic toxicological evidence (i.e., thyroid growth and thyroid hormonal changes)

indicated that e tofenprox was inducing a d isruption in the thyroid

- pituitary hormonal status; and

v. Rats are substantially more sensitive than humans to the development of thyroid follicular cell tumors in response to thyroid hormone imbalance. The overall weight

- of

- the

- evidence was

considered suffi cient to indicate that e tofenprox induced thyroid follicular tumors throug h an antithyroid mode of action. The quantification of carcinogenic potential is not applicable. Therefore, no risk quantification is required.



### 2. Non

- dietary exposure

a. Occupational exposure

Etofenprox for public health mosquito adulticide uses on food/feed commodities are to be applied by PCOs only, using ULV ground, aerial, or backpack applications. The potential exposures and associated risks for handlers mixing, load ing and applying etofenprox as a mosquito adulticide are based on the proposed label for RF2056 OL (etofenprox 20% liquid formulation). The maximum application rate is 0.007 lb ai/acre. Backpack applications may be made as a dilute or undiluted spray. App lication is not to be made to the same site more than once in three days, and no more than 2 times to a single site in any week. A maximum of 25 applications are allowed per year.

Short

- and intermediate

- term dermal and inhalation exposures are predicted for occupational handlers mixing, loading, and applying etofenprox at low volume by ground, aerial, or backpack equipment. Since no dermal toxicity endpoint was identified for etofenprox, only inhalation exposures are assessed. Since etofenprox

- specific e xposure data are not available, handler scenarios were assessed using

the Occupational Pesticide Handler Unit Exposure Surrogate Reference Table

- Revised March 2013 . The

occu pational handler exposure and risk estimates for etofenprox use as a ULV mosquito adulticide are

listed below.

Occupational Handler Exposure & Risk Estimates for Etofenprox Use as ULV Mosquito Adulticide

Short

- &

Intermediate

- Term Exposure Unit Exposure 1 (mg/lb ai handled) Application

Rate (lb ai/A) Units Treated 2 (A/day) Average Daily

Dose 3 (mg ai/kg bw/day) Short

- & Intermediate

Term MOE 4

Mixer/Loader

– Liquids (ULV)

– Open Loading for Ground Application 5

Inhalation 0.000219 0.007 3000 0.00005749 180,000

Mixer/Loader

– Liquids (ULV)

– Open Loading for Aerial Application

Inhalation 0.000219 0.007 7500 0.00014 74,000

Applicator

– Liquids (ULV)

– Ground 5

Inhalation 0.00471 0.007 3000 0.001236 8,600

Applicator

– Liquids (ULV)

– Aerial

Inhalation 0.0000049 0.007 7500 0.0000032 3,3000,000
Flagger

– Liquids (ULV)

– Aerial

Inhalation 0.00035 0.007 350 0.000011 990,000

Mixer/Loader/Applicator

– Liquids (ULV)

– Backpack Sprayer

Inhalation 0.00258 1.48 6 40 7 0.0019 5,600

1 Unit Exposure = mg ai/lb ai handled from the Occupational Pesticide Handler Unit Exposure Surrogate Reference Table

- Revised March 2013

. 2 Units Treated taken from Science Advisory Council for Exposure, Standard Operating Procedure 9.1, Standard Values for Daily Acres Treated in Agriculture, Rev. 25, September 2001.

3 Average Daily Dose (ADD) = Unit Exposure x Application Rate x Units Treated x Absorption Factor (inhalation 100%) ÷ Body Weight (80 kg).

4 Margin of Exposure (MOE) = NOAEL (mg/kg/day) ÷ ADD (mg/kg/day); where the NOAEL = 10.6 mg/kg/day for all durations of inhalation

exposure.

5 Exposure and risk for ULV ground equipment calculated based on parameters for open cab airblast sprays

6 lb a.i./gal (undiluted)

7 gallons/day

### Page 7 of 10 Since occupational post application activities are not expected with mosquito adulticide applications, no

asses sment was conducted.

Applications of etofenprox for mushroom production are to be applied as either a surface application using handheld equipment or as a fogging concentrate. The potential exposures and associated risks for handlers mixing, loading and applying etofenprox in mushroom production are based on the proposed label for RF2129 EC (etofenprox 16.2% liquid formulation). The maximum application rate by fogging equipment is 0.96 lb ai/acre. The maximum application rate using handheld equipment is 0 .22 lb ai/gallon.

Short

- and intermediate

- term dermal and inhalation exposures are predicted for occupational handlers mixing, loading, and applying etofenprox for mushroom production. Since no dermal toxicity endpoint was identified for etofenprox, onl y inhalation exposures are assessed. Since etofenprox

- specific exposure data are not available, handler scenarios were assessed using the Occupational Pesticide Handler Unit

E xposure Surrogate Reference Table

- Revised March 2013 . The occupational handler exposure and risk estimates for etofenprox use in mushroom production are listed below.

Occupational Handler Exposure & Risk Estimates for Etofenprox Use in Mushroom Product ion

Short

- &

Intermediate

- Term Exposure Unit Exposure 1 (mg/lb ai handled) Application

Rate (lb ai/A) Units Treated 2 (A/day) Average Daily

Dose 3 (mg ai/kg bw/day) Short

- & Intermediate

Term MOE 4

Mixer/Loader

– Liquids (concentrate)

– Fogger

Inhalation 0.000219 0.96 5 0.000013 810,000

Mixer/Loader/Applicator

– Liquids

– Manually

- Pressurized Handwand Sprayer

Inhalation 0.030 0.022 5 40 6 0.00033 32,000

Mixer/Loader/Applicator

– Liquids

– Backpack Sprayer

Inhalation 0.14 0.0225 406 0.0015 6,900

Mixer/Loader/Applicator

– Liquids

– Mechanically

- Pressurized Handgun Sprayer

Inhalation 0.12 0.0225 10006 0.033 320

1 Unit Exposure = mg ai/lb ai handled from the Occupational Pesticide Handler Unit Exposure Surrogate Reference Table

- Revised March 2013

. 2 Units Treated taken from Science Advisory Council for Exposure, Standard Operating Procedure 9.1, Standard Values for Daily A cres Treated in Agriculture, Rev. 25 , September 2001.

3 Average Daily Dose (ADD) = Unit Exposure x Application Rate x Units Treated x Absorption Factor (inhalation 100%) ÷ Body Weig ht (80 kg).

4 Margin of Exposure (MOE) = NOAEL (mg/kg/day) ÷ ADD (mg/kg/day); where the NOAEL = 10.6 mg/kg/da y for all durations of inhalation

exposure.

5 lb a.i./gallon

6 gallons/day

Since occupational post application activities are not expected with mosquito adulticide applications, no

assessment was conducted.



### b. Residential (Non

- occupational) exposure and risk

Since applications for public health mosquito control are to be made by professional personnel (i.e., not residential) a residential handler exposure assessment is not required; however, there are potential post application exposures to adults and children from the ULV fogging applications of etofenprox uses in the vicinity of residential dwellings. Based on the Health Effects Division review (HED: DP Barcode: 342643; J. Arthur; 06/09/08), all adult and children’s exposures from ULV aeri al applications of etofenprox result in MOEs greater than 100 and therefore do not exceed HED’s level of concern.



### D. Cumulative Effects

### Page 8 of 10 Cumulative effects from substances with a common mechanism of toxicity: Section 408(b)(2)(D)(v) of the

FFDCA requires that, when considering whether to establish, modify, or revoke a tolerance, the Agency consider ``available information'' concerning the cumulative effects of a particular pesticide's residues and

``other substances that have a common mechanism of toxicity.''

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to etofenprox and any other substances, and etofenprox does not appear to produce a toxic metabolite produced by other substances. Therefore for the purposes of this tolerance action, EPA has not assumed that etofenprox has a common mechanism of toxicity with other substances.

E

. Safety Factor for Infants and Ch ildren

In general, Section 408 of the FFDCA provides that EPA shall apply an additional ten

- fold margin of safety for infants and children in the case of threshold effects to account for prenatal and postnatal toxicity

a nd the completeness of the data base on toxicity and exposure unless EPA determines that a different margin of safety will be safe for infants and children. Margins of safety are incorporated into EPA risk assessments either directly through use of a MOE analysis or through using uncertainty (safety) factors in calculating a dose level that poses no appreciable risk to humans.

Developme ntal toxicity studies: A prenatal developmental toxicity study in rabbits showed no quantitative/qualitative evidence of increased susceptibility in offspring. In the rabbit study

, the developmental effects were seen at doses that resulted in maternal deaths at the high dose. A dditionally, the rabbit developmental study showed increased abortions, decreased maternal body weights, body weight gains and food consumption. In the rabbit study, the maternal LOAEL (300 milligram/kilogram/day (mg/kg/day)) is equal to the developmental LOAEL. In the 1

- generation/developmental study in rats, increased susceptibility in the offspring was not observed. In the rat developmental study, the maternal LOAEL was equal to the developmental LOAEL.

Reproductive toxicity study: The 2

- generation repr oduction study in rats did not show evidence of quantitative/qualitative susceptibility in offspring. In this study

, rats showed decreased pup weights, increased thyroid, liver and kidney weights with corresponding pathological changes in pups, and clinica l signs of pups during most of the lactation period which included body tremors, distended abdomen, lethargy, unsteady gait, and abnormal movements. However, except for thyroid weight in female pups, all of these effects occurred at the highest dose tested (HDT). The effects on organ weights carried over to the

adults of both the F 1 and F 2 generations with corresponding centrilobular hepatocyte enlargement and increased thyroidal epithelial height in the HDT group of the F 1 generation. At the high dose, par ents (F 0 ) had similar effects on their organs as the pups: increased liver, thyroid, and kidney weights with pathological changes in the kidney. The parental LOAEL was equal to the offspring LOAEL in the 2

- generation reproduction study in rats.

Pre natal a nd postnatal sensitivity: There is no indication of increased quantitative/qualitative evidence of susceptibility of the offspring in the developmental rat or rabbit studies or in the 2

- gen eration reproduction study in the rat. Developmental effects were s een at doses that caused maternal toxicity. No developmental

effects were seen in the rat 1

- generation/developmental study. In the 2

- generation reproduction toxicity study, there was no evidence of quantitative and qualitative susceptibility because the pr esence of toxicity in the offspring occurred at the level of parental toxicity (increased organs weights and associated pathological changes occurred in both the pups and parents). In the developmental neurotoxicity study in rats, the observed eye abnormal ities associated with body injuries could not be disassociated from possible

altered treatment

- related maternal behavior that resulted in injury to the pups.

### Page 9 of 10 Conclusion: The toxicology database for e tofenprox is essentially complete. The data are sufficie nt for endpoint selection for exposure/risk assessment scenarios and for evaluation of the requirements under the Food Quality Protection Act (FQPA). Evidence of quantitative and qualitative susceptibility of offspring

was not observed and therefore, the FQPA 10x safety factor was reduced to 1x.

F

. Aggregate Risks and Determination of Safety

There are a number of r egistered e tofenprox products. These include outdoor yard foggers, indoor crack and crevice, indoor total

- re lease foggers and cat spot

- on products , rice uses and as mosquito adulticides

. The proposed application in this submission amends the tolerance for ULV mosquito adulticide use to

food/feed commodities and establishes tolerances for residues of 

### fungi, edibl e, group 21 . The application

rate of 0.007 lb ai/A for mosquito adulticiding is identical to the previously approved mosquito adulticide

use. A ll handler and post

- application risks from the ULV mosquito adulticide use were found not to

exceed HED’s level of concern. The mushroom production use was also found not to exceed HED’s level

of concern.

1. Acute risk An acute risk assessment was not performed. No toxicological endpoint attributable to a single (acute) dietary exposure was identified. Therefore, acute risk from Etofenprox exposure to is not expected.

2. Chronic risk Using the exposure assumptions describe d in this unit for chronic exposure, it was concluded that exposure

to e tofenprox from food and water will utilize 1.1 % of the Rdf for the U.S. population, and 4.6% of the

Rfd for children 1

- 2 years old, the subpopulation at greatest exposure. Based on the use pattern, chronic residential exposure to residues of e tofenprox is not expected. Therefore, the aggregate exposure is not expected to exceed 100% of the Rfd

.

3. Short

- term risk

Short

- term aggregate exposure takes into account residential exposure plus chro nic exposure to food and

water . Etofenprox is currently registered for use(s) that could result in short

- term residential exposure and

it was determined that it is appropriate to aggregate chronic food and water and short

- term exposures for

e tofenprox

.

F ood, water

, and residential exposures aggregated result in combined MOEs that do not exceed the Agency's level of concern for aggregate exposure to food, water

, and residential uses. Therefore, short

term aggregate exposure is not expected to excee d the Agency's level of concern

.

4. Intermediate

- term risk

Intermediate

- term aggregate exposure takes into account non

- dietary, non

- occupational exposure plus chronic exposure to food and water . Etofenprox is currently registered for use(s) that could result in

i ntermediate

- term residential exposure

, and it was determined that it is appropriate to aggregate chronic

food and water and intermediate

- term exposures for e tofenprox

.

I ntermediate

- term aggregate MOEs do not exceed the Agency's level of concern for aggreg ate exposure to food, water, and res idential uses. Therefore, intermediate

- term aggregate exposure is not expected to exceed the Agency's level of concern.

5. Cancer risk Etofenprox has been classified as, `` N ot likely to be carcinogenic to humans at doses that do not alter rat thyroid hormone homeostasis.'' Therefore, e tofenprox is not expected to pose a cancer risk.

### Page 10 of 10 6. Determination of safety Based on these risk assessments, it is concluded that there is a reasonable certainty that no harm will result to the general population and to infants and children from aggregate exposure to e tofenprox residues.

G

. International Tolerances

Etofenprox is in the CODEX system with a residue definition of etofenprox for a variety of crops as

indicated in the table below:

Commodity Maximum Residue Limits (MRL) mg/kg Apple 0.6 Beans (dry) 0.05 Dried grapes (currant, raisins and sultanas) 8 Edible offal (mammalian) 0.05 Eggs 0.01 Grapes 4

Maize 0.05

Meat (from mammals other than marine mammals) 0.5

Milks 0.02

Nectarine 0.6

Peach 0.6

Pear 0.6 Poultry meat 0.01 Poultry, Edible offal of 0.01 Rape seed 0.01

Rice 0.01

Rice straw and fodder, Dry 0.05